br Our previous report showed that chronic H pylori
768
710
Our
previous
report
showed
that
chronic H pylori
significantly
upon hydrogen peroxide or di-tert-butyl
hy-
769
711
droperoxide treatment, but was unaltered upon NAC treat-
770
infection
significantly
increases
CAPZA1
expression in
712
ment (Figure 4C). These observations suggest that oxidative
771
the gastric mucosa
of
Mongolian
gerbils
and that
CAP-
713
stress induces CAPZA1 expression via enhanced histone H3
772
ZA1-overexpressing
cells
are
detected
throughout
the
714
acetylation of the CAPZA1 promoter.
gastric mucosal epithelium from gastric glands to gastric
715
H
pylori
infection
signi cantly
increased
CAPZA1
774
pits.
21
By contrast, H pylori infection does not up-regulate
fi
expression in the gastric mucosa of
Mongolian gerbils
775
CAPZA1 expression in AGS Ibrutinib in vitro, indicating that it
717
(Figure 5A). Malondialdehyde and protein carbonyl levels
776
does
not
directly induce
CAPZA1 expression in gastric
are used as biomarkers of oxidative stress. There was a
777
epithelial cells.
21
In the present study, we investigated how
significant linear correlation between CAPZA1 expression
778
CAPZA1 expression is induced in H pylori–infected gastric
mucosal epithelium. The inflammatory response in H pylo-
721
ri–infected gastric mucosa, which is induced via reactive
CAPZA1 expression and protein carbonylation (r ¼ 0.65;
780
722
oxygen species and reactive nitrogen species generated by
P ¼ .04) (Figure 5B). To visually assess the relationship
781
723
neutrophils and monocytes, contributes to the development
between oxidative stress and CAPZA1 overexpression in H
782
724
pylori–infected gastric epithelium, we performed immuno-
783
of H pylori–related disease.
28
On the other hand, CD44v9-
staining of 8-hydroxy-2’-deoxyguanosine, which is produced
784
positive cells show enhanced resistance to reactive oxygen
726
upon oxidative damage of the nucleoside deoxyguanosine
785
species owing to stabilization of the glutamate-cystine
727Q12
and then excreted extracellularly. CAPZA1-overexpressing
786
transporter xCT at the cytoplasmic membrane.3 Ishimoto
728
et al
29
proposed that chronic inflammation induced by H
cells
in
H
pylori–infected gastric
mucosa mainly
co-
787
localized
with 8-hydroxy-2’-deoxyguanosine–positive cells
788
pylori infection leads to the generation of CD44v9-positive
cells.
We
thus
hypothesized
that this
inflammatory
731
stress
induced by H
pylori infection
increases
CAPZA1
790
response contributes to the induction of CAPZA1 expres-
732
expression. We subsequently examined whether CD44v9
791
sion, leading to development of CD44v9-positive cells. To
733
expression was induced in CAPZA1-overexpressing cells in
792
investigate this, we examined changes in CAPZA1 expres-
734
H pylori–infected gastric mucosa. In gastric mucosa of 2 of 5
793
sion in AGS cells upon treatment with hydrogen peroxide or
735
Mongolian gerbils, CD44v9-positive
cells were
detected
794
di-tert-butyl peroxide. Treatment with hydrogen peroxide
736
among
CAPZA1-overexpressing cells,
indicating
that
795
or di-tert-butyl peroxide increased CAPZA1 expression in a
dose-dependent manner (Figure 4A). In addition, these in-
738
expression (Figure 6). When considered together with the
797
creases
were abrogated
by
N-acetylcysteine
(NAC) treat-
739
in vitro
H pylori infection data, adherence of H pylori to
798
ment (Figure 4B). We previously reported that alteration in
740
CAPZA1-overexpressing cells leading to CagA accumulation
799
the chromatin structure by acetylated histone H3 is involved
741
in H
pylori–infected gastric mucosa
is
considered to be
800
in induction of
CAPZA1
21
We
subsequently
742
expression.
required for the development of CD44v9-positive cells.
analyzed
alterations
in
the
chromatin
structure of the
We subsequently investigated the effect of eradication
802
CAPZA1 proximal promoter region in AGS cells treated with
744
therapy on the level of CAPZA1 expression by examining 5
803
hydrogen peroxide or di-tert-butyl peroxide by performing
745
patients with H pylori
infection and 5 patients who had
804
chromatin
immunoprecipitation
(ChIP)
with
an antibody